ENGINEERING PROTEIN MECHANICS - INHIBITION OF CONCERTED MOTIONS OF THE CELLULAR RETINOL-BINDING PROTEIN BY SITE-DIRECTED MUTAGENESIS

Recently we reported on the dynamic properties of the cellular retinol binding protein, a member of the fatty acid binding protein family. A few conserved glycines were identified as important for producing the conformational changes necessary for the uptake and release of retino l. Here, we describe a multidisciplinary analysis of a genetically eng ineered mutation of one of these glycines (Gly67), designed to inhibit an observed hinge bending motion. The correctly folded mutant protein is unable to bind retinol. Analysis of the molecular dynamics simulat ions of the mutant and wild type protein using the essential dynamics method shows that the mutation indeed inhibits the hinge bending motio ns which are important for retinol binding.